1. Technical Field
The present invention relates to a probe for detecting a polymorphism, a method of detecting a polymorphism, a method of evaluating the efficacy of a drug, and a reagent kit for detecting a polymorphism.
2. Related Art
The BRAF gene encodes the BRAF protein which is involved in intracellular signaling and cell growth. It is known that the intracellular signaling pathway becomes constitutively activated when the BRAF gene undergoes mutation such that the 600th amino acid of the BRAF protein is mutated from valine (V) to glutamic acid (E). Such a BRAF-activated mutant is called “V600E” and is observed in about 7% of human malignant tumors and about 60% of malignant melanomas (see, for example, Nature. (2010) Dec. 16; 468(7326): 973-7). Further, it has also been reported that advanced melanoma having a V600E mutation is effectively treated with, for example, the BRAF kinase inhibitor vemurafenib. When administering the BRAF kinase inhibitor vemurafenib, from the standpoints of the effectiveness and safety, it is necessary to detect the presence or absence of the V600E mutation in advance.
Methods have been developed by which the V600E mutation is measured accurately in a short time in an inexpensive and simple manner (see, for example, WO2011/071046 and Japanese Patent Application Laid-Open (JP-A) 2009-77712). In addition, methods of detecting a mutation in the BRAF gene using a PCR-RFLP method, a direct sequencing method, an HRMA method or the like are also known (see, for example, Endocr J. (2007) June 54(3): p. 399-405; Yonsei Med. J. (2009) April 30, 50(2): p. 266-'72; Am. J. Clin. Pathol. (2008) August, 130(2): p247-53).
At present, in addition to the V600E mutation, V600K, V600R and V600D mutations in which the 600th amino acid is mutated from valine to lysine (K), arginine (R) and aspartic acid (D), respectively, are known (see, for example, J. Transl. Med. (2010) Jul. 14, 8: p67). Further, V600G and V600M mutations in which the 600th amino acid is mutated to glycine (G) and methionine (M), respectively, are also known.